De-Souza, Evandro A;
Cummins, Nadia;
Taylor, Rebecca C;
(2022)
IRE-1 endoribonuclease activity declines early in C. elegans adulthood and is not rescued by reduced reproduction.
Frontiers in Aging
, 3
, Article 1044556. 10.3389/fragi.2022.1044556.
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Abstract
The proteome of a cell helps to define its functional specialization. Most proteins must be translated and properly folded to ensure their biological function, but with aging, animals lose their ability to maintain a correctly folded proteome. This leads to the accumulation of protein aggregates, decreased stress resistance, and the onset of age-related disorders. The unfolded protein response of the endoplasmic reticulum (UPRER) is a central protein quality control mechanism, the function of which is known to decline with age. Here, we show that age-related UPRER decline in Caenorhabditis elegans occurs at the onset of the reproductive period and is caused by a failure in IRE-1 endoribonuclease activities, affecting both the splicing of xbp-1 mRNA and regulated Ire1 dependent decay (RIDD) activity. Animals with a defect in germline development, previously shown to rescue the transcriptional activity of other stress responses during aging, do not show restored UPRER activation with age. This underlines the mechanistic difference between age-associated loss of UPRER activation and that of other stress responses in this system, and uncouples reproductive status from the activity of somatic maintenance pathways. These observations may aid in the development of strategies that aim to overcome the proteostasis decline observed with aging.
| Type: | Article |
|---|---|
| Title: | IRE-1 endoribonuclease activity declines early in C. elegans adulthood and is not rescued by reduced reproduction |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fragi.2022.1044556 |
| Publisher version: | https://doi.org/10.3389/fragi.2022.1044556 |
| Language: | English |
| Additional information: | © 2022 De-Souza, Cummins and Taylor. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | UPR, unfolded protein response, proteostasis, cell stress, stress response, C. elegans, aging, IRE1 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10162829 |
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